Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences
Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences
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DOI：
10.1016/j.pbb.2016.11.005
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Viveros, Maria-Paz
中科院分区：
文献类型：
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作者：
Marco, Eva M.;Ballesta, Javier Antonio;Viveros, Maria-Paz
酒精使用障碍和抑郁症是高度共存的，并且这两种疾病都表现出重要的性二态性。在这里，我们的目的是调查 Wistar 大鼠（用作抑郁症动物模型）在 6 周慢性轻度应激 (CMS) 后的自愿饮酒量。研究人员对雄性和雌性大鼠进行了研究，并分析了额叶皮层（FCx）和海马结构（HF）中几种分子标记的变化。 CMS 在雄性和雌性动物的强迫游泳试验中诱发抑郁样反应，增加不动时间，但不影响快感缺乏（蔗糖偏好测试）或运动活动（洞板）；仅 CMS 雄性的体重增加和食物摄入量有所减少。连续 4 天以两瓶选择范例（20% 乙醇与自来水）评估自愿饮酒量；与雄性动物相比，雌性对酒精表现出更高的偏好。特别是，与 CMS 雄性动物相比，CMS 雌性动物的饮酒量显着更高。值得注意的是，在暴露于 CMS 的雄性和雌性动物中观察到 FCx 内 NCAM-140 KDa 表达水平（降低）、GFAP 和 CB1R 表达（增加）以及 HF PSD-95 水平（增加）的类似变化。然而，据报道，雄性和雌性的 FCx、HF CB1R 表达中的突触素 (SYN) 蛋白水平存在对比效应（雄性动物中下降，但雌性动物中增加）；而 HF 中 NCAM-140 KDa 蛋白水平则观察到相反的模式。仅在 CMS 雌性的 HF 中观察到 CB2R 表达的减少。目前的研究表明，雄性和雌性动物在后期自愿饮酒方面可能会受到 CMS 的不同影响。在这种初步方法中，HF 内的皮质 SYN 和 NCAM-140 KDa、CB1R 和 CB2R 表达已成为解释这种行为性别差异的潜在候选者。然而，抑郁症与酗酒之间的关系仍值得进一步研究。 (C) 2016 年，爱思唯尔公司出版
Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimor-phisms. Here, we aimed to investigate voluntary alcohol consumption after 6 weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test-increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140 KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140 KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140 KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression-alcoholism relationship still deserves further investigation. (C) 2016 Published by Elsevier Inc.